Using phage peptide library screening, we identified peptide-encoding phages that selectively home to the inflamed central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis (MS). A phage peptide display library encoding cyclic 9-amino-acid random peptides was first screened ex-vivo for binding to the CNS tissue of EAE mice, followed by in vivo screening in the diseased mice. Phage insert sequences that were present at a higher frequency in the CNS of EAE mice than in the normal (control) mice were identified by DNA sequencing. One of the phages selected in this manner, denoted as MS-1, was shown to selectively recognize CNS tissue in EAE mice. Individually cloned phages with this insert preferentially homed to EAE CNS after an intravenous injection. Similarly, systemically-administered fluorescence-labeled synthetic MS-1 peptide showed selective accumulation in the spinal cord of EAE mice. We suggest that peptide MS-1 might be useful for targeted drug delivery to CNS in EAE/MS.

中文翻译：

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一种新型的CNS-homing肽，可靶向实验性自身免疫性脑脊髓炎中的神经炎性病变。

使用噬菌体肽库筛选，我们确定了编码肽的噬菌体，这些噬菌体选择性地归入患有实验性自身免疫性脑脊髓炎（EAE）（人多发性硬化症（MS）模型）的小鼠发炎的中枢神经系统（CNS）。首先对离体筛选编码环状9-氨基酸随机肽的噬菌体肽展示文库与EAE小鼠的CNS组织结合，然后在患病小鼠中进行体内筛选。通过DNA测序鉴定出在EAE小鼠的CNS中比正常（对照）小鼠中频率更高的噬菌体插入序列。已显示以这种方式选择的一种噬菌体，称为MS-1，可选择性识别EAE小鼠的CNS组织。静脉注射后，带有该插入片段的单独克隆的噬菌体优选归巢于EAE CNS。同样，全身施用的荧光标记的合成MS-1肽在EAE小鼠的脊髓中显示出选择性积累。我们建议肽MS-1可能对EAE / MS中靶向药物递送至CNS有用。